Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Dramatic improvements in the multi-agent chemotherapy of children with ALL resulted in cure rates of 70-75%. Despite recent improvements in therapy, perhaps 1 in 5 will eventually suffer leukemic relapse. Currently, the major challenge in the treatment of childhood ALL is to cure patients who have relapsed while on therapy or shortly after cessation of therapy. Treatment of these children has generally been either intensive chemotherapy to achieve a second remission and subsequent use of either nonablative chemotherapy or ablative radiochemotherapy followed by BMT. Intensification of cytotoxic therapy using conventional drugs will likely cause overlapping toxicities and may result in delays which may decrease the intensity of therapy. Immunotoxin therapy provides an alternative strategy which may enhance antileukemic effect with nonoverlapping toxicities. B43-PAP is a dose-escalation study. Three patients will be treated at each dose level. B43-PAP will be given to children with relapsed ALL or high risk ALL in first remission. Children will be treated in courses consisting of 3 cycles. B43-PAP will be given in the hospital for 5 consecutive days, followed by 7 days of rest, then repeated two more times, followed by 2 months of rest A patient may receive a total of 36 cycles (up to 3 years).